Ecstasy's Legacy

J. W. Stewart
It now appears that the fleeting sense of euphoria resulting from a hit of the club drug comes with a very long-term cost. That price, exacted through some strange system of neurochemical accounting, is a lack of one of the key brain chemicals contributing to feelings of well-being and happiness.

Images: NATIONAL INSTITUTE ON DRUG ABUSE

BRAIN CHANGES appear prominently in positron emission tomography (PET) scans of Ecstasy users as well as people who abstain. Drug users(right), though, have far less serotonin activity, as is indicated by the dark areas, compared to the controls (left). New studies show that this difference may contribute to permanent brain damage.

In a paper appearing in the July 25 issue of Neurology, Stephen Kish of the Centre for Addiction and Mental Health in Toronto reports that Ecstasy causes a severe depletion in the brain of serotonin--the very same neurotransmitter that many antidepressant medications aim to augment.

To reach his conclusions, Kish compared the brain of a 26-year-old man who had died from a drug overdose to those of 11 subjects who did not use drugs. "The levels of serotonin and another chemical associated with serotonin were 50 to 80 percent lower in the brain of the Ecstasy user," Kish notes. Serotonin was particularly scarce in the striatal area of the brain, which helps coordinate movement.

These consequences make sense, Kish says, considering the drug's observed behavioral effects. Ecstasy, known chemically as < 3-4 methylenedioxymethamphetamine (MDMA), is related to mescaline, MDA and methamphetamine. And, like these other drugs, it prompts nerve cells to release a flood of serotonin. Initially, this release would be expected to bring about the increased awareness of emotion and intimacy and self-confidence that Ecstasy users report. The ensuing chemical low tide could explain the depression users describe when they are coming down.

"Conclusions based on a single case can only be tentative," Kish urges."Of course, these findings should be confirmed through additional studies." But there is good reason to believe that further work will back Kish up. Although his study is the first to demonstrate dramatic and lasting brain damage, it is not the first to forge some sort of link between Ecstasy and serotonin.

George Ricaurte and his wife Una D. McCann, both at the Johns Hopkins Medical Institutions and experts in MDMA's effects, have with their colleagues performed numerous studies in humans and animals. In one, they compared PET scans of 14 Ecstasy users to 15 controls and found that the first group had far fewer serotonin transporters, spots on neurons responsible for reabsorbing the chemical. They found a similar trend in an imaging study of baboons and, when examining the monkeys' brain tissue, discovered an actual loss of serotonin nerve endings.

The researchers went on to find functional consequences of the physical differences after giving memory tests to 24 Ecstasy users and 24 people who had never used the drug. Drug users--even those who had not taken Ecstasy recently--found it much more difficult to remember what they had seen or heard during the tests. "Our study extends the MDMA-induced memory impairment to at least two weeks since last drug use," commented Karen Bolla of Johns Hopkins. Also, it showed that the impairment was not due to withdrawal and was heavily dose-dependent.

It will take many more investigations to fully explain the toll Ecstasy takes on the brain, but a clear idea of the kinds of costs involved is emerging. "The message from these studies," says Joseph Frascella of the National Institute on Drug Abuse, "is that MDMA does change the brain, and it looks like there are functional consequences to these changes." In other words, rave parties just got a lot more expensive.